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https://www.readbyqxmd.com/read/28627683/regulatory-role-of-tumor-necrosis-factor-receptor-associated-factor-6-in-breast-cancer-by-activating-the-protein-kinase-b-glycogen-synthase-kinase-3%C3%AE-signaling-pathway
#1
Hongyu Shen, Liangpeng Li, Sujin Yang, Dandan Wang, Siying Zhou, Xiu Chen, Jinhai Tang
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626608/c-kit-modifies-the-inflammatory-status-of-smooth-muscle-cells
#2
Lei Song, Laisel Martinez, Zachary M Zigmond, Diana R Hernandez, Roberta M Lassance-Soares, Guillermo Selman, Roberto I Vazquez-Padron
BACKGROUND: c-Kit is a receptor tyrosine kinase present in multiple cell types, including vascular smooth muscle cells (SMC). However, little is known about how c-Kit influences SMC biology and vascular pathogenesis. METHODS: High-throughput microarray assays and in silico pathway analysis were used to identify differentially expressed genes between primary c-Kit deficient (Kit(W/W-v)) and control (Kit(+/+)) SMC. Quantitative real-time RT-PCR and functional assays further confirmed the differences in gene expression and pro-inflammatory pathway regulation between both SMC populations...
2017: PeerJ
https://www.readbyqxmd.com/read/28616865/isoacteoside-a-dihydroxyphenylethyl-glycoside-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization
#3
Hongwei Gao, Yankun Cui, Naixin Kang, Xin Liu, Yanli Liu, Yue Zou, Ziyu Zhang, Xiaoran Li, Shilin Yang, Ji Li, Chunming Wang, Qiong-Ming Xu, Xiuping Chen
BACKGROUND AND PURPOSE: Isoacteoside (ISO) is a phenylethanoid isolated from Monochasma savatieri Franch. ex Maxim., which is an anti-inflammatory herb widely used in traditional Chinese medicine. However, the exact mechanism of the anti-inflammatory activity of ISO is not completely understood. In this study, its anti-inflammatory mechanism in mouse macrophages was elucidated. EXPERIMENTAL APPROACH: The expression of the NF-κB pathway, MAPK pathway, iNOS, TNF-α, IL-6 and IL-1β was evaluated using western blotting, qRT-PCR or ELISA...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28615527/a20-functions-as-mediator-in-tnf%C3%AE-induced-injury-of-human-umbilical-vein-endothelial-cells-through-tak1-dependent-mapk-enos-pathway
#4
Lei Li, Bingqing Huang, Shiyang Song, Hareshwaree Sohun, Zhiheng Rao, Luyuan Tao, Qike Jin, Jingjing Zeng, Rongzhou Wu, Kangting Ji, Jiafeng Lin, Lianpin Wu, Maoping Chu
A20, a negative regulator of nuclear factor κB signaling, has been shown to attenuate atherosclerotic events. Transforming growth factor beta-activated kinase 1 (TAK1) plays a critical role in TNFα-induced atherosclerosis via endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the study, we investigated the hypothesis that A20 protected endothelial cell injury induced by TNFα through modulating eNOS activity and TAK1 signalling. Human umbilical vein endothelial cells (HUVECs) were stimulated by TNFα...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608226/blocking-rhoa-rock-inhibits-the-pathogenesis-of-pemphigus-vulgaris-by-suppressing-oxidative-stress-and-apoptosis-through-tak1-nod2-mediated-nf-%C3%AE%C2%BAb-pathway
#5
Junqin Liang, Xuewen Zeng, Yilinuer Halifu, Wenjing Chen, Fengxia Hu, Peng Wang, Huan Zhang, Xiaojing Kang
Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein...
June 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28607106/ubash3a-mediates-risk-for-type-1-diabetes-through-inhibition-of-t-cell-receptor-induced-nf-%C3%AE%C2%BAb-signaling
#6
Yan Ge, Taylor K Paisie, Jeremy R B Newman, Lauren M McIntyre, Patrick Concannon
Although over 40 type 1 diabetes (T1D) risk loci have been mapped in humans, the causative genes and variants for T1D are largely unknown. Here, we investigated a candidate gene in the 21q22.3 risk locus-UBASH3A, which is primarily expressed in T cells where it is thought to play a largely redundant role. Genetic variants in UBASH3A have been shown to be associated with several autoimmune diseases in addition to T1D. However, the molecular mechanism underlying these genetic associations is unresolved. Our study reveals a previously unrecognized role of UBASH3A in human T cells: UBASH3A attenuates the NF-κB signal transduction upon T cell receptor (TCR) stimulation by specifically suppressing the activation of the IKK complex...
June 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28603043/tak1-as-the-mediator-in-the-protective-effect-of-propofol-on-renal-interstitial-fibrosis-induced-by-ischemia-reperfusion-injury
#7
Huiping Wu, Jun Zhou, Weiming Ou, Yun Li, Meifang Liu, Chengxiang Yang
Ischemia-reperfusion injury (IRI), which is a major cause of acute and chronic renal dysfunction, induces both apoptosis and fibrotic processes. The mitogen-activated protein kinase kinase kinase transforming growth factor-β-activated kinase 1 (TAK1) was implicated in the processes of inflammation and fibrosis. The protective effect of propofol on renal functionality after acute kidney injury (AKI) in mice has been identified, whereas the mechanisms underlying fibrosis induced by kidney injury remain obscure...
June 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28592892/noncanocial-cell-death-program-independent-of-caspase-activation-cascade-and-necroptotic-modules-is-elicited-by-loss-of-tgf%C3%AE-activated-kinase-1
#8
September R Mihaly, Yosuke Sakamachi, Jun Ninomiya-Tsuji, Sho Morioka
Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis. Indeed, necroptosis is triggered by caspase inhibition to ensure cell death. Here we identified a previously uncharacterized cell death pathway regulated by TAK1, which is unexpectedly provoked by inhibition of caspase activity and necroptosis cascades...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28577391/shrimp-tab1-interacts-with-tak1-and-p38-and-activates-the-host-innate-immune-response-to-bacterial-infection
#9
Sheng Wang, Mengqiao Li, Bin Yin, Haoyang Li, Bang Xiao, Kai Lǚ, Zhijian Huang, Sedong Li, Jianguo He, Chaozheng Li
Mammalian TAB1 has been previously identified as transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) binding protein, which functions as the activator of TAK1 and p38. This report, for the first time, identified and characterized the homolog of TAB1 in shrimp, to be specific, the homolog gene from Litopenaeus vannamei, containing a 1560-bp open reading frame (ORF) that encoded a putative protein of 519 amino acids with the conserved PP2Cc (Serine/threonine phosphatases, family 2C, catalytic) domain in N-terminal and a TAK1 binding motif in C-terminus, has been cloned and named LvTAB1...
May 31, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28573848/polyphenols-from-lonicera-caerulea-l-berry-inhibit-lps-induced-inflammation-through-dual-modulation-of-inflammatory-and-antioxidant-mediators
#10
Shusong Wu, Satoshi Yano, Jihua Chen, Ayami Hisanaga, Kozue Sakao, Xi He, Jianhua He, De-Xing Hou
Lonicera caerulea L. berry polyphenols (LCBP) are considered as major components for the bioactivities. This study aimed to clarify the molecular mechanisms by monitoring inflammatory and antioxidant mediator actions in lipopolysaccharide (LPS)-induced mouse paw edema and macrophage cell model. LCBP significantly attenuated LPS-induced paw edema (3.0 ± 0.1 to 2.8 ± 0.1 mm, P < 0.05) and reduced (P < 0.05) serum levels of monocytes chemotactic protein-1 (MCP-1, 100.9 ± 2.3 to 58.3 ± 14.5 ng/ml), interleukin (IL)-10 (1596...
June 2, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28572508/cardioprotective-role-of-traf2-by-suppressing-apoptosis-and-necroptosis
#11
Xiaoyun Guo, Haifeng Yin, Lei Li, Yi Chen, Jing Li, Jessica Doan, Rachel N Steinmetz, Qinghang Liu
Background -Programed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. Methods -We examined the role of Traf2 (TNF receptor-associated factor 2) in regulating myocardial necroptosis and remodeling using genetic mouse models...
June 1, 2017: Circulation
https://www.readbyqxmd.com/read/28569204/tgf%C3%AE-1-induced-smad2-3-and-smad1-5-phosphorylation-are-both-alk5-kinase-dependent-in-primary-chondrocytes-and-mediated-by-tak1-kinase-activity
#12
Arjan van Caam, Wojciech Madej, Amaya Garcia de Vinuesa, Marie-José Goumans, Peter Ten Dijke, Esmeralda Blaney Davidson, Peter van der Kraan
BACKGROUND: Dysregulated transforming growth factor β (TGFβ) signaling is implicated in osteoarthritis development, making normalizing TGFβ signaling a possible therapy. Theoretically, this can be achieved with small molecule inhibitors specifically targeting the various TGFβ receptors and downstream mediators. In this study we explore in primary chondrocytes the use of small molecule inhibitors to target TGFβ-induced pSmad1/5/9-, pSmad2/3- and TGFβ-activated kinase 1 (TAK1)-dependent signaling...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28566127/retraction-notice-to-modification-of-tak1-by-o-linked-n-acetylglucosamine-facilitates-tak1-activation-and-promotes-m1-macrophage-polarization-cellular-signalling-28-2016-1742-1752
#13
Dongmei Zhang, Zhiwei Xu, Tao Tao, Xiaojuan Liu, Xiaolei Sun, Yuhong Ji, Lijian Han, Huiyuan Qiu, Guizhou Zhu, Yifen Shen, Liang Zhu, Aiguo Shen
No abstract text is available yet for this article.
August 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28560435/microrna-146a-promotes-gastric-cancer-cell-apoptosis-by-targeting-transforming-growth-factor-%C3%AE-activated-kinase-1
#14
Yiming Chen, Bin Zhou, Lubai Xu, Hengwei Fan, Junqin Xie, Dan Wang
Accumulating evidence suggests that microRNA (miR)-146a functions as an oncogene or tumor suppressor in various cancers. However, the role of miR‑146a in gastric cancer (GC) remains to be elucidated. The present study investigated the function of miR‑146a in GC cells. The results of the present study revealed that miR‑146a modulates GC cell apoptosis. Overexpression of miR‑146a significantly increased apoptosis of SGC‑7901 cells, whereas inhibition of miR‑146a protected cells from apoptosis. miR‑146a expression in GC cells was inversely correlated with transforming growth factor β‑activated kinase 1 (TAK1) expression, at the mRNA and protein levels...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28553282/co-inflammatory-roles-of-tgf%C3%AE-1-in-the-presence-of-tnf%C3%AE-drive-a-pro-inflammatory-fate-in-mesenchymal-stem-cells
#15
Shalom Lerrer, Yulia Liubomirski, Alexander Bott, Khalid Abnaof, Nino Oren, Afsheen Yousaf, Cindy Körner, Tsipi Meshel, Stefan Wiemann, Adit Ben-Baruch
High plasticity is a hallmark of mesenchymal stem cells (MSCs), and as such, their differentiation and activities may be shaped by factors of their microenvironment. Bones, tumors, and cardiomyopathy are examples of niches and conditions that contain MSCs and are enriched with tumor necrosis factor α (TNFα) and transforming growth factor β1 (TGFβ1). These two cytokines are generally considered as having opposing roles in regulating immunity and inflammation (pro- and anti-inflammatory, respectively). Here, we performed global gene expression analysis of human bone marrow-derived MSCs and identified overlap in half of the transcriptional programs that were modified by TNFα and TGFβ1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28553204/leucine-rich-repeat-kinase-2-lrrk2-stimulates-il-1%C3%AE-mediated-inflammatory-signaling-through-phosphorylation-of-rcan1
#16
Kyung A Han, Lang Yoo, Jee Y Sung, Sun A Chung, Ji W Um, Hyeyoung Kim, Wongi Seol, Kwang C Chung
Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling through modulation of several intracellular targets of interleukins in immune cells. In the present study, we report that LRRK2 phosphorylates RCAN1 (RCAN1-1S) and is markedly up-regulated during interleukin-1β (IL-1β) treatment...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28539327/quantitative-phospho-proteomic-analysis-of-tnf%C3%AE-nf%C3%AE%C2%BAb-signaling-reveals-a-role-for-ripk1-phosphorylation-in-suppressing-necrotic-cell-death
#17
Firaz Mohideen, Joao Paolo, Alban Ordureau, Steve P Gygi, J Wade Harper
TNFα is a potent inducer of inflammation due to its ability to promote gene expression, in part via the NFκB pathway. Moreover, in some contexts, TNFα promotes Caspase-dependent apoptosis or RIPK1/RIPK3/MLKL-dependent necrosis. Engagement of the TNF Receptor Signaling Complex (TNF-RSC), which contains multiple kinase activities, promotes phosphorylation of several downstream components, including TAK1, IKKα/IKKβ, IκBα, and NFκB. However, immediate downstream phosphorylation events occurring in response to TNFα signaling are poorly understood at a proteome-wide level...
May 24, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28537667/mechanism-of-the-high-coagulation-state-of-breast-cancer-tissue-factor
#18
X-K Mi, Q-R Liu, L Zhu, M-X Sang, L-R Guo, B-E Shan
OBJECTIVE: We conducted this study to analyze the mechanism behind the high coagulation state induced by circulating plasma microparticle tissue factor (MP-TF) in patients with breast cancer. PATIENTS AND METHODS: 87 cases of breast cancer patients (10 cases of TNM stage I, 16 cases of II, 32 cases of III, 29 cases of IV; 8 cases of pathological type in situ carcinoma, 15 cases of ductal carcinoma, 64 cases of invasive cancer) were used as the observation group and 20 cases of benign breast lesions were used as the control group to compare MP-TF levels of plasma and coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer body (D-D) level and NF-κB signaling pathway index including P50, p65, TAK1 and IκBα levels...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28532672/molecular-insights-into-the-differences-in-anti-inflammatory-activities-of-green-tea-catechins-on-il-1%C3%AE-signaling-in-rheumatoid-arthritis-synovial-fibroblasts
#19
Sabrina Fechtner, Anil Singh, Mukesh Chourasia, Salahuddin Ahmed
In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#20
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
July 2017: Nature Immunology
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